Beta Blockade and the HeartBeta Blockade and the Heart

John Hakim, M.DJohn Hakim, M.D

Cardiology FellowCardiology Fellow

West Virginia UniversityWest Virginia University

Division of CardiologyDivision of Cardiology

Beta Blocker Heart Attack TrialBeta Blocker Heart Attack Trial

Randomized 4000 Patients to Placebo Vs. Randomized 4000 Patients to Placebo Vs. PropranololPropranolol

20% Reduction in Mortality in Propranolol 20% Reduction in Mortality in Propranolol groupgroup

Despite a 17% rise in Triglycerides and a Despite a 17% rise in Triglycerides and a 6% rise in LDL6% rise in LDL

Beta Blockers in ACUTE MIBeta Blockers in ACUTE MI

Beta Blockers Reduce pain, and reduce Beta Blockers Reduce pain, and reduce need for analgesics presumably by reducing need for analgesics presumably by reducing ischemiaischemia

Most useful in patients with sinus Most useful in patients with sinus tachycardia and HTN post MItachycardia and HTN post MI

Beta Blockers in ACUTE MIBeta Blockers in ACUTE MIProtocol (Braunwald)Protocol (Braunwald)

Exclude patients with Heart Failure (10 cm rales above Exclude patients with Heart Failure (10 cm rales above diaphragm), hypotension <90mmHG, Bradycardia <60 diaphragm), hypotension <90mmHG, Bradycardia <60 bpm, and Heart Block.bpm, and Heart Block.

Metoprolol in three 5mg boluses q 5 min*Metoprolol in three 5mg boluses q 5 min* Stop if HR <60 or SBP <100mmHgStop if HR <60 or SBP <100mmHg If stable, give oral metoprolol 50mg q6h x 2 daysIf stable, give oral metoprolol 50mg q6h x 2 days Then switch to 100mg BID or Toprol XLThen switch to 100mg BID or Toprol XL (*IV (*IV

esmolol useful in patient with relative esmolol useful in patient with relative contraindication.)contraindication.)

What not to give Post Acute MIWhat not to give Post Acute MI

Unlike Beta Blockers, calcium antagonists Unlike Beta Blockers, calcium antagonists are of little value in AMI and may, in fact, are of little value in AMI and may, in fact, be hazardous.be hazardous.

Effects of Beta Blockers Post MIEffects of Beta Blockers Post MI

Immediate: reduces cardiac index, heart rate and Immediate: reduces cardiac index, heart rate and blood pressure. Net effect is to reduce myocardial blood pressure. Net effect is to reduce myocardial oxygen consumption/minute/beat. (Reduces Chest oxygen consumption/minute/beat. (Reduces Chest Pain)Pain)

Reduces infarct Size in Acute MIReduces infarct Size in Acute MI Diminishes circulating levels of free fatty acids by Diminishes circulating levels of free fatty acids by

antagonizing lipolytic effects of catecholamines. antagonizing lipolytic effects of catecholamines. (FFA augment O(FFA augment O2 2 consumption and increases consumption and increases

incidence of arryhthmias.incidence of arryhthmias.

Effects of Beta Blockers Post MIEffects of Beta Blockers Post MI(Pre-Thrombolytic Era)(Pre-Thrombolytic Era)

ISIS-1ISIS-1– 16,000 patients randomized16,000 patients randomized– reduction of mortality among patients reduction of mortality among patients

randomized to IV atenolol Vs. placebo.randomized to IV atenolol Vs. placebo. Meta analysis of 27 trials (27,000+ patients) IV Meta analysis of 27 trials (27,000+ patients) IV

followed by oral beta blockersfollowed by oral beta blockers– 15% relative reduction in mortality, non fatal 15% relative reduction in mortality, non fatal

reinfarction, and nonfatal cardiac arrestreinfarction, and nonfatal cardiac arrest

Effects of Beta Blockers Post MIEffects of Beta Blockers Post MI

TIMI-II trial (Thrombolytics in MI)TIMI-II trial (Thrombolytics in MI)– Recurrent ischemiaRecurrent ischemia and and reinfarctionreinfarction were were

reduced by immediate vs. delayed use of reduced by immediate vs. delayed use of metoprolol.metoprolol.

– mortalitymortality and and LV functionLV function were were not not improvedimproved by immediate metoprolol. by immediate metoprolol.

– Therefore beta-blockers are beneficial, but may Therefore beta-blockers are beneficial, but may not enhance the salvage of myocardium due to not enhance the salvage of myocardium due to early reperfusion.early reperfusion.

Effects of Beta Blockers Post MIEffects of Beta Blockers Post MICurrent RecommendationsCurrent Recommendations

Patients with hyperdynamic state Patients with hyperdynamic state ( sinus tachycardia, HTN, no CHF or ( sinus tachycardia, HTN, no CHF or bronchospasm, no heart block)bronchospasm, no heart block)

Patients seen in the first 4 hours of their MIPatients seen in the first 4 hours of their MI Regardless of whether thrombolytics are Regardless of whether thrombolytics are

usedused Beta-Blockers indicated for people with Beta-Blockers indicated for people with

persistent or recurrent ischemic painpersistent or recurrent ischemic pain

Beta Blockers and Idiopathic Beta Blockers and Idiopathic Dilated CardiomyopathyDilated Cardiomyopathy

Chronic Beta-Blockers increase the number Chronic Beta-Blockers increase the number of Beta adrenergic receptors on the Heartof Beta adrenergic receptors on the Heart

Reduced ischemia and more efficient oxygen Reduced ischemia and more efficient oxygen utilization utilization (Study done w/ metoprolol)(Study done w/ metoprolol)

Detectable improvement in Cardiac Output Detectable improvement in Cardiac Output (and EF) after three months.(and EF) after three months.

Long term structural changes of decline in Long term structural changes of decline in LV volume and Mass after 12-18 months.LV volume and Mass after 12-18 months.

Other Beta Blocker IndicationsOther Beta Blocker Indications

Arrhythmias associated withArrhythmias associated withthyrotoxicosis, pheochromocytoma thyrotoxicosis, pheochromocytoma – excess catecholamine state.excess catecholamine state.

Arrhythmias initiated by excercise or Arrhythmias initiated by excercise or emotion often respond to propranololemotion often respond to propranolol

Metoprolol may be helpful in controlling Metoprolol may be helpful in controlling rate of multifocal atrial tachycardiarate of multifocal atrial tachycardia

Question:Question:

Peri-operative myocardial ischemia is the Peri-operative myocardial ischemia is the single most important reversible risk factor single most important reversible risk factor for mortality and cardiovascular for mortality and cardiovascular complications annually.complications annually.

Is there any way to prevent perioperative Is there any way to prevent perioperative myocardial ischemia during non cardiac myocardial ischemia during non cardiac therapy?therapy?

Perioperative Cardiovascular Perioperative Cardiovascular Morbidity and MortalityMorbidity and Mortality

In patients who are at risk for coronary In patients who are at risk for coronary artery disease who must undergo non-artery disease who must undergo non-cardiac surgery, treatment with atenolol cardiac surgery, treatment with atenolol during hospitalization can reduce mortality during hospitalization can reduce mortality and the incidence of cardiovascular and the incidence of cardiovascular complications for as long as 2 years after complications for as long as 2 years after surgery. surgery.

(N Eng J Med 1996;335:1713-20)(N Eng J Med 1996;335:1713-20)

Perioperative Cardiovascular Perioperative Cardiovascular Morbidity and MortalityMorbidity and Mortality

In patients with CAD standard practice is to In patients with CAD standard practice is to control heart rate pre-op and intra-op.control heart rate pre-op and intra-op.

Post-op tachycardia may precipitate ischemiaPost-op tachycardia may precipitate ischemia Beta-blockade can modulate the post-op Beta-blockade can modulate the post-op

sympathetic response.sympathetic response. Preventing ischemia prevents morbidity and Preventing ischemia prevents morbidity and

mortality.mortality.